Category: Ataxia
Objective: We present an instructive case of a 41-year-old woman with idiopathic late onset cerebellar ataxia.
Background: Identifying the cause of idiopathic late onset cerebellar ataxia (ILOCA) is challenging. While history and examination can narrow the diagnosis, genetic testing has made it possible to diagnose rare, atypical ataxia phenotypes. The significance of many variants remains to be determined.
Method: We describe a 41-year-old woman with ILOCA, summarizing her history, examination, and extensive laboratory and genetic testing. Additional workup was recommended based on genetic test results (skin biopsy with fibroblast cell culture and filipin staining; and plasma oxysterols level), which confirmed the diagnosis.
Results: Our patient had pure cerebellar features on exam without vertical supranuclear palsy or family history of neurological illnesses. Workup for metabolic and autoimmune causes of ataxia, and genetic testing for spinocerebellar ataxia repeat expansions was negative. Exome sequencing revealed a maternally inherited pathogenic variant and a paternally inherited likely pathogenic variant in the NPC1 gene. Her initial NPC Suspicion Index tool suggested low probability of NPC. However, the gene result led us to proceed to skin biopsy which showed cholesterol esterification to be 54% of normal control cells, and determination of plasma oxysterols which were elevated. She had silent thrombocytopenia, for which we requested abdominal ultrasound showing splenomegaly.
Conclusion: We present an atypical case of NPC presenting as ILOCA which required genetic testing to point to the diagnosis, and targeted disease-specific studies for diagnostic confirmation. She is now on miglustat therapy, a potential disease-modifying treatment for NPC, and she is eligible for future NPC clinical trials. Genetic testing is an essential tool in the evaluation and management of patients with slowly evolving idiopathic cerebellar ataxia.
To cite this abstract in AMA style:
G. Crotty, J.Y Chen, D. Brockman, J. Schmahmann. New pathogenic mutation in the Niemann-Pick C (NPC) Type 1 gene: Confirmation by diagnostic workup of NPC in a 41-year-old woman with idiopathic late onset cerebellar ataxia (ILOCA) [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/new-pathogenic-mutation-in-the-niemann-pick-c-npc-type-1-gene-confirmation-by-diagnostic-workup-of-npc-in-a-41-year-old-woman-with-idiopathic-late-onset-cerebellar-ataxia-iloca/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/new-pathogenic-mutation-in-the-niemann-pick-c-npc-type-1-gene-confirmation-by-diagnostic-workup-of-npc-in-a-41-year-old-woman-with-idiopathic-late-onset-cerebellar-ataxia-iloca/